Carvedilol has structure as shown in formula 1. Carvedilol is disclosed in U.S. Pat. No. 4,503,067 (assigned to Boehringer Mannheim, GmbH, Germany) and it is chemically known as (±)-1-(9H-carbazol-4-yloxy)-3-[[2(2-methoxyphenoxy)ethyl]amino]-2-propanol.

Carvedilol is a racemic mixture of R(+) and S(−) enantiomers. Both enantiomers are nonselective β-adrenergic blocking agent with α1 blocking activity while S(−) enantiomer also has non-selective β-adrenoreceptor blocking activity. Carvedilol is used for treatment of hypertension, congestive heart failure and angina.
There are several patents and patent applications that are directed to crystalline salts and solvates thereof and also to their preparation.
The product U.S. Pat. No. 4,503,067 (Boehringer Mannheim) describes salts of carvedilol with acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulphuric acid, acetic acid, citric acid, maleic acid or benzoic acid.
The U.S. Pat. No. 6,515,010 covers carvedilol methane sulfonate.
Another U.S. Pat. No. 7,056,942 assigned to Teva discloses crystalline carvedilol hydrochloride hydrate.
The patent application US 2005/240,027 (assigned to SmithKline Beecham) disclose crystalline carvedilol dihydrogen phosphate hemihydrate, carvedilol dihydrogen phosphate dihydrate, carvedilol dihydrogen phosphate, carvedilol dihydrogen phosphate methanol solvate and carvedilol hydrogen phosphate.
In the patent application US 2005/277,689 (assigned to GlaxoSmithKline) crystalline salt, forms or solvate of carvedilol selected from the group consisting of carvedilol mandelate, lactate, maleate, sulfate, glutarate, mesylate, phosphate, citrate, hydrogen bromide, oxalate, hydrochloride, benzoate and corresponding forms or solvates thereof are described.
The patent application US 2005/261,355 (assigned to SB Pharmco) covers carvedilol hydrobromide monohydrate and carvedilol hydrobromide.
The patent application US 2005/148,779 (GlaxoSmithKline) claims crystalline carvedilol monocitrate monohydrate
We have filed an Indian patent application 292/KOL/2007 dated 27 Feb. 2007 in Indian Patent Office on amorphous form of carvedilol dihydrogen phosphate and the process for its preparation. The amorphous form obtained by the process described in this application has glass transition temperature below 60° C. The amorphous solids in general having low glass transition temperature not only create complications during formulation but also has stability related problems on storage. The glass transition temperature is the temperature, below which the physical properties of amorphous materials vary in a manner similar to those of a crystalline phase (glassy state), and above which amorphous materials behave like liquids (rubbery state). A materials glass transition temperature is the temperature below which molecules have little relative mobility. Thus, there exist a need to develop stable amorphous form of carvedilol dihydrogen phosphate which have improved characteristics.
The synthetic exploration of novel crystalline forms, amorphous form and/or solvates thereof of a pharmaceutically active compound provides a possibility to a organic chemist, to obtain a new form or solvate that has improved characteristics such as bulk density, particle size, stability, solubility in aqueous solution and ease of processing in the formulation for preparing suitable pharmaceutical dosages.
In case of carvedilol dihydrogen phosphate, the patent as well publication literature lack in providing information on stable amorphous form of carvedilol dihydrogen phosphate, thereby indicating poor attention given by the synthetic chemists for its isolation and preparation. The present invention is directed to the stable amorphous form of carvedilol dihydrogen phosphate and to also to the development of process for its preparation.